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Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The SeDeM-ODT expert system is designed to assess the suitability of the pharmaceutical ingredients for their conversion into an orodispersible formulation by direct compression. The tool can be utilized to select the most appropriate excipients that improve the compressibility and buccodispersibility of the formulation. Objective: This study aimed to utilize the SeDeM-ODT expert system to evaluate the performance of superdisintegrants and select an appropriate superdisntegrant for Doxylamine Succinate orodispersible formulation. Method: The SeDeM-ODT expert system scrutinized the excipients to develop an orodispersible Doxylamine Succinate formulation. Among the 15 parameters of the tool, some of them were determined through experimental work, while the remaining were calculated through the experimental values of other parameters. The central composite design approach was used for formulation development. The prepared powder blends were compressed using the direct compression method and evaluated for different parameters (hardness, thickness, diameter, friability, weight variation, water absorption ratio, wetting time, and disintegration time). Results: The results of the SeDeM-ODT expert system were correlated with the values obtained by the post-compression tests. The Crospovidone formulation (F7) was found to be an optimized formulation as it disintegrated quickly compared with the other formulations containing other superdisintegtrants. The results perfectly endorsed the SeDeM-ODT expert system evaluation, as Crospovidone showed the highest IGCB value of 6.396. Conclusion: The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The assessment proved Crospovidone to produce quicker disintegration in Doxylamine Succinate orodispersible formulation. [ABSTRACT FROM AUTHOR]

Dry-route manufacturing technology development poses challenges to pharmaceutical technology research specialists, relying on active substance characteristics, excipient selection, and parameter optimization. Amongst various technological possibilities high shear mixing generally ensures dosage uniformity and tablet dissolution through influential shear forces, potentially enhancing dry powder blend processability. This study explores the processability of a placebo formulation within the quality by design framework to address some of the aforementioned challenges. A 24 full-factorial experimental design was used to assess the manufacturability of a placebo formulation via high shear mixing. The effect of impeller and chopper speed, high shear mixing time, and homogenization/lubrication times on powder blend rheology and compression properties was investigated. The findings of the present study showed that product critical quality attributes like resistance to crushing or disintegration time are mainly dependent on the mixing efficiency translated by the impeller speed and high shear mixing time. Software augmented process development enabled the attainment of the design space, ensuring the fulfilment of desired product performance criteria. Furthermore, the study has also shown that the careful selection of excipients is crucial in the case of dry-route manufacturing technologies, as sodium lauryl sulphate can noticeably influence the processability of powder blends due to its lubricant properties. Considering the advantages and challenges raised by high-shear mixing, software aided data analysis can further augment the formulation, scale-up and lifecycle management of products developed using this technological process. [ABSTRACT FROM AUTHOR]

Polyherbal chewable tablets of Phyllanthus emblica and Glycyrrhiza glabra were developed with the objective to formulate an effective, safe and convenient dosage form for acid-related disorders. A standard calibration curve was constructed for Polyherbal extracts through UV-Spectrophotometry, achieving an absorbance maximum at 275 nm. Compatibility between the drug and excipients was examined through FTIR studies. Various pre-compression parameters, like bulk density, tapped density, compressibility index, Hausner's ratio and angle of repose, were assessed for the powder blend. The tablets were evaluated for post-compression parameters, such as thickness, hardness, friability, and weight variation and disintegration time. The drug release study was conducted in vitro. The acid-neutralizing capacity of the formulated batches was compared with marketed formulations. The calibration curve showed a high correlation coefficient (r2=0.9972), suggesting accuracy and reliability. FTIR analysis confirmed the compatibility between the drug and excipients. Pre-compression studies revealed an acceptable range for all parameters, indicating good flow properties. For instance, Carr's Index for all batches varied from 14.31% to 24.41%, and the angle of repose ranged from 33.7 to 35.21 degrees. Post-compression parameters were within the standard limits with hardness between 4.9 to 6.1 kg/cm2 and friability less than 1% for all batches. In vitro drug release showed a gradual increase over time with PF9 achieving 98.63% release at 60 min. The acid-neutralization capacity was highest for the combined extract at 27.83±0.34 mEq/g and PF9 batch at 28.12±0.43 mEq/g, demonstrating their effectiveness in neutralizing acid. The study successfully formulated a Polyherbal chewable tablet with optimized pre and post-compression parameters. The tablet exhibited promising in vitro drug release and an efficient acid-neutralizing capacity. It holds potential as an effective treatment option for acid-related disorders. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the mechanical stresses and strains acting on pharmaceutical glass tubing vials during freezing and thawing of model pharmaceutical formulations. Strain measurements were conducted inside of a laboratory-scale freeze-dryer using a custom wireless sensor. In both sucrose and trehalose formulations at concentrations between 5 % and 20 % w/v, the strain measurements initially increased before peaking in magnitude at temperatures close to the respective glass transition temperatures of the maximally freeze concentrated solutes, Tg'. We attribute this behavior to a shift in the mechanical properties of the frozen system from a purely elastic glass below Tg' to a viscoelastic rubber-like material above Tg'. That is, when the interstitial region becomes mechanically compliant at temperature above Tg'. The outputs were less predictable below 5 % w/v and tended to exhibit two separate peaks in strain output, one near the equilibrium melting temperature of pure ice and the other near Tg'. The peaks merged at concentrations between 4 and 5 % w/v where the largest strain magnitude was observed. The strain on primary packaging has traditionally been applied to evaluate the risk of damage or breakage due to, for example, crystallization of excipients. However, data collected during this study suggest there may be utility in formulation design or as a process analytical technology to minimize potentially destabilizing stresses and strains in the frozen formulation. [ABSTRACT FROM AUTHOR]

Excipients, or inactive ingredients, are a frequent cause of medication intolerance and allergy. Patients and clinicians concerned about medication allergies and sensitivities rely on the U.S. National Library of Medicine's DailyMed for accurate lists of excipients. Based on our anecdotal discovery of several examples of excipient omissions, we wished to examine the accuracy of DailyMed's listings more systematically in a sample of commonly prescribed medications. The objective of the study is to identify the frequency of inconsistency of excipient reporting within the DailyMed website. We performed a database audit of the Structured Product Labeling XML file provided by the drug manufacturer to the Food and Drug Administration and DailyMed for two randomly selected formulations of each of 50 commonly prescribed medications. For each of the 100 formulations, we compared the excipients listed in the "Description" to those in the "Ingredients and Appearance" sections in DailyMed. The Structured Product Labeling data file provided by the drug manufacturer contained internal inconsistencies of excipients in 39% of the formulations examined. Despite the use of Structured Product Labeling, the drug manufacturer's medication labels provided to the FDA and reported by DailyMed often contain conflicting information about inactive ingredients. Patients with allergies and excipient sensitivity should be aware of these discrepancies and consult multiple sections of the label to identify potential allergy-inducing inactive ingredients. [ABSTRACT FROM AUTHOR]

This in vitro study investigated color stability of two photo-polymerized nano-filled and nano-hybrid composite resins in different polymerization modes immersed in different staining solutions before and after brushing. Disc-shaped specimens (n = 120) were prepared from two composite resins based on filler particle size: nano-filled (Filtek Z350, shade A1, 3M ESPE) and nano-hybrid (Spectra ST-HV, shade A1, Dentsply Sirona) composite resins (n = 60 per composite type). Specimens of each resin type were photopolymerized using the following polymerization modes: LED conventional, ramp, and pulse (n = 20 specimens per resin type and LED mode). After preparation, baseline color of the specimens was evaluated using a spectrophotometer (Easyshade V, VITA), and color change was evaluated using the CIE L*a*b* formula. Specimens were soaked in distilled water for 4 weeks in separate containers. The specimens from each polymerization-mode group were separated into two groups of 10 specimens; one group was stored in tea and the other group was stored in cola, each 1 hour daily for 4 weeks. After 4 weeks, the color was measured again. The specimens were brushed for 2 minutes under 200-g weight using an electronically powered toothbrush on the polymerized side of the specimen. The color was reevaluated immediately after brushing. Color-difference data (ΔE) between groups were analyzed by one-way analysis of variance for main comparison and by independent t test for color change after brushing. Nano-filled composite resin was more color-stable than nano-hybrid composite resin (P < .001), regardless of the staining media. For both composite resin types, the conventional polymerization method produced a more color-stable result (P < .0001). ΔE after brushing was reduced significantly (P < .0001). Both staining solutions have significant effects on color change, with tea staining more than cola (P < .0001). Nanofilled composite resin had greater color stability than nano-hybrid composite resin after immersion in staining solutions. Polymerization mode influences the color stability of both composite resin types. [ABSTRACT FROM AUTHOR]

Microneedles, a novel transdermal delivery system, were designed to improve drug delivery and address the challenges typically encountered with traditional injection practices. Discovering new and safe excipients for microneedle coating to replace existing chemical surfactants is advantageous to minimize their side effect on viable tissues. However, some side effects have also been observed for this application. The vast majority of studies suggest that using synthetic surfactants in microneedle formulations may result in skin irritation among other adverse effects. Hence, increasing knowledge about these components and their potential impacts on skin paves the way for finding preventive strategies to improve their application safety and potential efficacy. Biosurfactants, which are naturally produced surface active microbial products, are proposed as an alternative to synthetic surfactants with reduced side effects. The current review sheds light on potential and regulatory aspects of biosurfactants as safe excipients in the coating of microneedles.

Pediatric drug expression presents different challenges and freedoms on account of the singular corporeal traits and enlightening stages of adolescents. Developing age-appropriate formulations makes necessary a deep understanding of pediatric pharmacokinetics and pharmacodynamics, in addition to the security and productiveness characterizations of cures. This paper surveys the standards and practices complicated in pediatric drug expression, stressing the significance of the portion of the drug or other consumable veracity, palatability, and ease of presidency. It reviews differing portions of drugs or other consumable forms, containing spoken fluids, capable of disintegration tablets, and tiny tablets, and focal points the act of excipients in guaranteeing balance and reputation. Additionally, this paper addresses supervisory directions and the importance of including pediatric subjects and caregivers in the expression process to embellish devotion and healing effects. By checking current progress and case studies, this paper underlines the distracting need for tailor-made pediatric formulations to correct pediatric healthcare conditions. Future guidance in pediatric drug expression is labeled, accompanying a devoted effort to change the way that 3D publication, novel childbirth methods, and embodied cure approaches. This paper aims to determine an inclusive survey of pediatric drug expression, contribution observations, and methods for optimizing drug analysis. [ABSTRACT FROM AUTHOR]

Thermal stability attributes including unfolding onset (T onset) and mid-point (T m) are often utilized for efficient development of monoclonal antibody (mAb) products during lead selection and formulation screening workflows. An assumption of direct correlation between thermal and kinetic physical stability underpins this basic approach. While literature reports have substantiated this general approach under specific conditions, clear exceptions have been highlighted alongside. Herein, a set of mAbs formulated under diverse solution conditions to generate a broad array of thermal and kinetic stability profiles were systematically analyzed. Sequence modifications in the Fc region were purposefully engineered to generate a set of low-melting mAbs. A diverse set of excipients were subsequently utilized and shown to modulate the T m over a wide range. While a general correlation between high T m and low aggregation rate was observed under accelerated conditions, the predictive utility of T m under relevant product storage conditions was inadequate at best. Critically, T m data did not correlate with long-term aggregation rates under refrigerated or room temperature conditions. Even under accelerated conditions, T m appeared to be a poor predictor of aggregation once it exceeded the solution storage temperature (40°C) by ∼15°C, similar to conditions routinely encountered in the development of canonical mAbs (T m > 60°C). Pitfalls of simplistic correlative approaches are discussed in the context of practical biologics product development. [ABSTRACT FROM AUTHOR]

The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bi-directional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. No antioxidant increased drug permeability, while the positive control sodium lauryl sulfate always increased drug permeability. Results support that any of the ten antioxidants, up to at least 10 mg, can be added to a solid oral dosage form without modulating passive drug intestinal permeability. Additional considerations are also discussed. [ABSTRACT FROM AUTHOR]

Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community. [ABSTRACT FROM AUTHOR]

Co-processed superdisintegrants have emerged as key excipients in pharmaceutical formulation development, offering solutions to challenges related to poor solubility, bioavailability, and patient compliance. This comprehensive review article provides an in-depth analysis of the principles, mechanisms, manufacturing techniques, and applications of co-processed superdisintegrants in drug delivery systems. The review highlights the role of co-processed excipients in enhancing dissolution kinetics, improving formulation efficiency, and enabling innovative drug delivery platforms such as personalized medicine and combination therapies. Regulatory considerations, quality standards, and future directions for research and innovation in this field are also discussed. Through a synthesis of current literature and insights into emerging trends, this review aims to provide researchers, formulation scientists, and pharmaceutical professionals with a comprehensive understanding of the potential and challenges associated with co-processed superdisintegrants in pharmaceutical formulations. Ultimately, the integration of co-processed excipients into formulation development holds promise for advancing drug delivery technology, improving therapeutic outcomes, and addressing unmet medical needs in patient care. [ABSTRACT FROM AUTHOR]

The paper highlights the necessity for a robust regulatory framework for assessing nanomedicines and their off-patent counterparts, termed as nanosimilar, which could be considered as 'similar' to the prototype nanomedicine,based on essential criteria describing the 'similarity'. The term 'similarity' should be focused on criteria that describe nanocarriers, encompassing their physicochemical, thermodynamic, morphological, and biological properties, including surface interactions and pharmacokinetics. Nanocarriers can be regarded as advanced self-assembled excipients (ASAEs) due to their complexity and chaotic behavior and should be evaluated by using essential criteria in order for off-patent nanomedicines be termed as nanosimilars, from a regulatory perspective. Collaboration between the pharmaceutical industry, regulatory bodies, and artificial intelligence (AI) startups is pivotal for the precise characterization and approval processes for nanomedicines and nanosimilars and embracing innovative tools and terminology facilitates the development of a sustainable regulatory framework, ensuring safety and efficacy. This crucial shift toward precision R&D practices addresses the complexity inherent in nanocarriers, paving the way for therapeutic advancements with economic benefits. [ABSTRACT FROM AUTHOR]

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations. [ABSTRACT FROM AUTHOR]

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures. [ABSTRACT FROM AUTHOR]

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box–Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved Cmax, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets. [ABSTRACT FROM AUTHOR]

Dyes have conventionally been used in medicine for staining cells, tissues, and organelles. Since these compounds are also known as photosensitizers (PSs) which exhibit photoresponsivity upon photon illumination, there is a high desire towards formulating these molecules into nanoparticles (NPs) to achieve improved delivery efficiency and enhanced stability for novel imaging and therapeutic applications. Furthermore, it has been shown that some of the photophysical properties of these molecules can be altered upon NP formation thereby playing a major role in the outcome of their application. In this review, we primarily focus on introducing dye categories, their formulation strategies and how these strategies affect their photophysical properties in the context of photothermal and non‐photothermal applications. More specifically, the most recent progress showing the potential of dye supramolecular assemblies in modalities such as photoacoustic and fluorescence imaging, photothermal and photodynamic therapies as well as their employment in photoablation as a novel modality will be outlined. Aside from their photophysical activity, we delve shortly into the emerging application of dyes as drug stabilizing agents where these molecules are used together with aggregator molecules to form stable nanoparticles. [ABSTRACT FROM AUTHOR]

Biological macromolecules, encompassing proteins, nucleic acids, lipids, and carbohydrates, have garnered increasing attention as tethering excipients within the realms of pharmaceuticals and biotechnology. This concise appraisal offers a comprehensive overview of their multifaceted role, highlighting the latest advancements in their applications. Biological macromolecules, long regarded as fundamental components of life, have transitioned into pivotal agents that contribute significantly to drug development, drug formulation stability and the optimization of pharmacokinetic profiles. This review delineates how these macromolecules serve as integral players in the enhancement of drug delivery systems, enabling controlled release, targeted delivery, and improved bioavailability. Furthermore, they play a critical role in the stabilization of sensitive compounds, preserving their efficacy and extending their shelf life. Additionally, the interactions between macromolecules and therapeutic agents are pivotal in mitigating issues of solubility and bioavailability, further propelling their utility as excipients. Despite these promising attributes, challenges such as immunogenicity, scalability, and regulatory compliance persist. Navigating these hurdles necessitates a concerted effort from researchers, engineers, and regulatory bodies alike. In conclusion, biological macromolecules stand as formidable contenders in the field of tethering excipients. Their versatile applications in drug delivery, formulation stability, and pharmacokinetic enhancement hold the promise of revolutionizing the pharmaceutical and biotechnological landscapes. To realize this potential fully, the scientific community must continue to probe their intricacies, address challenges proactively, and foster collaborative efforts to ensure their seamless integration into the future of healthcare and therapeutics. Ultimately, the enduring impact of biological macromolecules on patient care is poised to be transformative and far-reaching. [ABSTRACT FROM AUTHOR]

Background: The compounding of extemporaneous preparations has historically been an essential part of the pharmacist's role, and, even today, its importance is recognized in all regulatory frameworks worldwide. The paediatric age group is known to be a therapeutic orphan, due to the low availability of formulations adapted to this population. There are potential dangers involved in treating paediatric patients with drugs approved for adults, or, more generally, off-label prescription medicines, since the excipients may be not suitable for children. As a result, the prescription of extemporaneous preparations is a common practice among paediatricians. Objective: Knowing cardiovascular diseases are currently the main cause of mortality in Haiti, the objective of this study was to develop a suitable paediatric oral liquid formulation of spironolactone with simple and low-cost excipients, and with an easy set-up method. This is in order to make the preparation suitable for the preparation in hospital or community pharmacies in those countries - even with limited resources- where it is necessary to administer spironolactone to paediatric patients. Methods: For the formulation being studied, in addition to the quality according to the directives set out in the European Pharmacopoeia, the stability was evaluated to assure adequate validity for therapeutic uses. For the evaluation of the uniformity of the suspension content, a standard procedure was developed through a HPLC method. The suspension samples were also analysed with a spectrophotometric assay. Results: The uniformity of content results confirmed that the concentration of the active molecule in each suspension was consistent. In addition, no variation in the expected concentration greater than 10% was detected after 90 days. Concerning pH, from the data, it can be observed that no sample underwent a significant variation in pH over time. Conclusion: We chose to focus our research on the development of a suspension with a very simple composition and a simple preparation procedure, while bearing in mind the quality of the finished product must be guaranteed. The preparation procedures should always be congruous with the equipment usually available in a community or hospital pharmacy's compounding laboratory, in whatever part of the world it is located. [ABSTRACT FROM AUTHOR]

UV Spectrophotometric method has been developed to determine Gliclazide in bulk pure and tablet forms. It is a simple, accurate, reproducible, rapid and less time-consuming method. The maximum wavelength of the drug was found to be 232nm. Beer Lamberts' law was obeyed in the concentration range of 2-20 µg/ml. (LOD)The limit of detection and limit of qualification (LOQ) was found to be 0.16 µg/ml and 0.50 µg/ml from this method per cent recovery of the drug was found to be 99.30% which indicates no interaction of the excipients. This method was found accurate, simple, precise and rapid for determination of tablet dosage form. [ABSTRACT FROM AUTHOR]

Microneedles, a novel transdermal delivery system, were designed to improve drug delivery and address the challenges typically encountered with traditional injection practices. Discovering new and safe excipients for microneedle coating to replace existing chemical surfactants is advantageous to minimize their side effect on viable tissues. However, some side effects have also been observed for this application. The vast majority of studies suggest that using synthetic surfactants in microneedle formulations may result in skin irritation among other adverse effects. Hence, increasing knowledge about these components and their potential impacts on skin paves the way for finding preventive strategies to improve their application safety and potential efficacy. Biosurfactants, which are naturally produced surface active microbial products, are proposed as an alternative to synthetic surfactants with reduced side effects. The current review sheds light on potential and regulatory aspects of biosurfactants as safe excipients in the coating of microneedles. [ABSTRACT FROM AUTHOR]

Oral diseases encompassing conditions such as oral cancer, periodontitis, and endodontic infections pose significant challenges due to the oral cavity's susceptibility to pathogenic bacteria and infectious agents. Saliva, a key component of the oral environment, can compromise drug efficacy during oral disease treatment by diluting drug formulations and reducing drug-site interactions. Thus, it is imperative to develop effective drug delivery methods. Stimuli-responsive nanocomposite hydrogels offer a promising solution by adapting to changes in environmental conditions during disease states, thereby enabling targeted drug delivery. These smart drug delivery systems have the potential to enhance drug efficacy, minimize adverse reactions, reduce administration frequency, and improve patient compliance, thus facilitating a faster recovery. This review explores various types of stimuli-responsive nanocomposite hydrogels tailored for smart drug delivery, with a specific focus on their applications in managing oral diseases. [ABSTRACT FROM AUTHOR]

Preformulation investigations into the development of drug formulations, encompassing considerations related to the structure of the drug, excipients, composition, and physical attributes are crucial. This phase is pivotal in ensuring the ultimate success of nanoemulsion development. The objective of this study was to evaluate and define the properties of bedaquiline (BDQ) and the necessary excipients for the formulation of self-emulsifying BDQ-loaded nanoemulsions. To determine the saturation solubility of BDQ in various oils, an in-house validated HPLC method was used. Fourier transform infrared spectroscopy was utilised to identify and evaluate the compatibility between BDQ and the selected excipients. The water titration method was used to construct phase diagrams to identify the type of structure that resulted following emulsification and to characterise the behaviour of mixtures along dilution paths. The solubility studies revealed that BDQ exhibited the highest solubility in olive oil, with a solubility of 3.45 ± 0.041 mg/ml. The design space led to the formation of emulsions categorised as Winsor products. Importantly, the FTIR data indicated the absence of any potential interactions between BDQ and the chosen excipients. The preformulation studies were successful and facilitated the selection of compatible and suitable excipients for the formulation of BDQ-loaded nanoemulsions. [ABSTRACT FROM AUTHOR]

A spectrophotometric method has been developed for the determination of certain amine-phenol-containing drugs, namely, adrenaline, phenylephrine hydrochloride, and terbutaline sulfate. The method depends on the formation of new products by the reaction of drugs with the Gibbs reagent (2,6-dichloroquinone-4-chloroamide) in a basic borate buffer medium with a pH value of 11. The products were measured at 475, 652.5, and 547 nm for the aforementioned drugs, respectively. Beer–Lambert law was obeyed in the ranges of 0.3–9.5, 0.5–17, and 0.5–55 µg/mL with average recovery of 101.10, 99.13, and 99.78% and a relative standard deviation of ≤3.31%, respectively. The method was free from excipient interferences and applied successfully for the assay of the studied drugs in their pharmaceutical formulations. The resulting products were found in the ratio of 1 : 1. [ABSTRACT FROM AUTHOR]

Drug release plays a crucial role in drug delivery. While current formulation approaches are capable of coarse-tuning the release profile, their precision and reproducibility are limited by the physicochemical properties of the excipients and active pharmaceutical ingredient (API). Innovative and advanced approaches are urgently needed, especially for site-specific targeting of drugs and to address their pharmacological requirements for optimal therapy. The 5 × 5 × 0.6 mm3 piezoelectric micropump developed by Fraunhofer EMFT was designed to enable precise drug delivery in a low volume format. In this study, we investigated the ability of the micropump to deliver solutions of highly soluble APIs using a wide range of customized pump profiles. Additionally, we examined the ability of the micropump to deliver suspensions containing various defined particle sizes. While results for suspensions indicate that pumping performance is highly dependent on the size and concentration of the suspended particles, results with API solutions demonstrate high precision and reproducibility of release, coupled with maximum flexibility in the release profile of the API. The piezoelectric micropump thus lays the cornerstone in the development of a wide range of innovative drug delivery profiles, enabling customized release profiles to be programmed and thus paving the way to fully personalized medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

The composition and technology for obtaining a solid dosed stable dosage form of a promising representative of the class of nitrogen monoxide (NO) donors, an anionic tetranitrosyl iron complex with thiosulfate ligands Na2[Fe2(S2O3)2(NO)4]·4H2O, were developed. The rate of NO generation by the complex could be modulated by using different types of excipients or by varying their concentrations. Albumin was found to be the optimal prolonging agent in the manufacture of this dosage form. The developed dosage form expanded the arsenal of long-acting NO-donor medicines used to treat socially significant diseases. [ABSTRACT FROM AUTHOR]

A simple, reproducible, and rapid kinetic method for the S-Carboxymethyl-L-cysteine/Carbocisteine (CCys) determination has been proposed and linked to CCys quantification in pharmaceutical preparations. The method is based on the inhibitory feature of Carbocisteine. CCys forms a stable complex with Hg2+ and reduces actual Hg2+ concentration and ultimately the rate of reaction between 2,2'-Bipyridine (Bipy) and [Fe(CN)6]4- catalyzed by Hg2+. Under the optimized reaction conditions with I = 0.1 mole dm-3 (KNO3), [Bipy] = 1.5 × 10–4 mole dm-3, Temp = 25.0 × 0.2°C, pH 3.8 × 0.03, [Hg+2] = 1.0 × 10–5 mole dm-3, and [[Fe(CN)6]4-] = 4.0 × 10–3 mole dm-3, a fixed time of 8 and 13 min was selected to compute the absorbance at 400 nm corresponding to the ultimate reaction product [FeBipy(CN)5]3-. With the proposed kinetic spectrophotometric method, the micro-level quantification of CCys in distinct water samples can be done down to 1.0 × 10–6 mole dm-3. The developed procedure is highly reproducible and can be efficiently used to quantitatively estimate CCys in the drug samples with high accuracy. The general additives present in drugs do not substantially interfere in the determination of CCys even up to 1000 times with [CCys]. [ABSTRACT FROM AUTHOR]

Sugars have long been used as stabilizing excipients for protein-based therapeutics during the development and production process. Incorporating stabilizing agents, such as sucrose and trehalose into dry formulations is a common strategy approved by the US FDA. However, single-sugar formulations may not be sufficient for diverse medicinal products, necessitating the blending of excipients to improve stability, dissolution, and patient acceptability. Our goal is to comprehensively understand the impact of excipients, focusing on the impact of various sugar types on formulation stability, and to explore the effectiveness of incorporating additional excipients such as amino acids, surfactants, and polyols, to further enhance protein stability. The review begins with an overview of sugars' used in proteins stabilization and the blending of excipients. It discusses the limitation of single-sugar formulations and explores alternatives such as oligo- or polysaccharides. The mechanism underlying sugar and excipient combinations is elucidated, emphasizing the benefits of blending multiple excipients for stabilizing therapeutic protein. Our findings demonstrate that excipients blending presents a promising strategy for improving the stability of sugar-stabilized therapeutic proteins. Combining sugars with other excipients such as amino acids and polyols effectively enhances formulation stability. Optimization of excipients ratios and quantities is crucial for achieving the desired stability profile for each specific protein. Considering the impact of excipients on stabilization is essential in therapeutic proteins development. Employing blends of various excipients in different ratios and quantities ensures appropriate stability and functionality of the protein formulations. [ABSTRACT FROM AUTHOR]

Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties. [ABSTRACT FROM AUTHOR]

In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0∼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery. [ABSTRACT FROM AUTHOR]

Levothyroxine is a drug with a narrow therapeutic index. Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability, which can result in major health problems. However, the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed.In this study, we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes. Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry (UHPLC-DIA-HRMS) was employed.UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products, but also the presence of non-expected components in the formulations. Among these, we identified compounds resulting from reactions between mannitol and other excipients, such as citric acid, stearate, and palmitate, or from reactions between an excipient and an active pharmaceutical ingredient, such as levothyroxine-lactose adduct. In addition to these compounds, undeclared phospholipids were also found in three formulations. This non-targeted approach is not common in pharmaceutical quality control analysis. Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3–5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold. [ABSTRACT FROM AUTHOR]

There has recently been growing interest in exploring the potential of direct compression (DC) method of tableting as an alternative to the conventional granulation technique. This approach involves straightforward powder mixing and compression, resulting in time and cost savings, and has successfully been applied to various drugs. However, drugs require good micromeritic qualities, such as flowability, good reproducible compression behaviour to be directly compressed because it affects its in-vitro and in-vivo performance. Since many active pharmaceutical ingredients lack these qualities, the crystallo co-agglomeration technique hasemergedas a potential area of research for particle design, utilised in the development of active ingredients best suited for direct compression of tablet dosage forms. Pure metronidazole exhibited significantly higher Carr's index, Hausner's ratio, and angle of repose of 41.93°±1.05, indicating cohesiveness and irregular shape of the crystals. Whereas the crystallo-co-agglomerates were found to have an angle of repose of 29.33°±0.96, denoting an improvement in the flowability of the agglomerated crystals. Improvements in mechanical handling parameters was revealed in metronidazole co-agglomerate tablets produced with DC excipients (F1, F2). These tablets were found to be more robust and of higher quality compared to those formulated using pure metronidazole (F4, F5, F6), which were of no significant difference with metronidazole formulated via wet granulation method (F7, F8, F10, F11). In-vitro dissolution studies of metronidazole co-agglomerates tablets showed no significant difference in the percentage drug release profilebetween tablets produced via direct compression and wet granulation method. Thus, the crystallo co-agglomeration technique can be effectively used in the formulation of metronidazole tablets by direct compression using Avicel® and Prosolv®, presenting an efficient and streamlined approach to tablet manufacturing. [ABSTRACT FROM AUTHOR]

Oral tablets containing solubilized drug in the presence of appropriate excipients may give us an immediate release of the drug. Phospholipid solid dispersion (PSD) is a branch of solid dispersion in which phospholipid acts as a hydrophilic polymer in the presence of a suitable adsorbent to enhance the solubility of poorly soluble drugs. The anti-hyperlipidemic drug Atorvastatin (ATR) is an example of such drug, as it belongs to the class II group according to the biopharmaceutical classification system (BCS) with low bioavailability due to its low solubility. Phosphatidylcholine in combination with magnesium aluminum silicate as an adsorbent in a ratio of ATR: PC: MAS 1:3:4 was used to prepare ATR PSD by the solvent evaporation method, the product showed acceptable physical properties and utilized for the preparation of immediate-release tablets (IRTs) of ATR. Ten formulas of ATR-IRTs were prepared by direct compression method using different types and concentrations of diluents (Avicel®PH102, Avicel®PH101, and starch) and superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) and evaluated for their drug content, weight variation, hardness, friability, in vitro disintegration time and dissolution profile. The tablets formula (T10) that were prepared with ATR-PSD and Avicel®PH102 as a diluent and Croscarmellose Sodium (CCS) 5% w/w as super disintegrant show the shortest disintegration time (DT) (38 ±1 sec.) and best drug release (91% within 15 min) in 0.05M phosphate buffer (pH 6.8). [ABSTRACT FROM AUTHOR]

Teaching chemistry and biology students about biologics design remains challenging despite its increasing importance in pharmaceutical development. Monoclonal antibodies, commonly called mAbs, are the most popular biologics. They have been developed into drugs to treat various diseases in the past decades. Multiple challenges exist for designing proper formulations to stabilize mAbs, such as preventing aggregation and mitigating viscosity. Molecular modeling and simulations can improve pharmaceutical products by examining the interactions between mAbs and other compounds, such as excipients. To introduce students to biopharmaceuticals, eight students at the Stevens Institute of Technology participated in a semester‐long course to learn the challenges of pharmaceutical development and different computational skills to study biologics design. The students started with a limited background in this field. Throughout one semester, they were introduced to various literature and software tools for modeling antibodies and studying their interactions with excipients. This paper aims to develop a course structure to be replicated at other universities and institutions to teach biopharmaceutical development to students. [ABSTRACT FROM AUTHOR]

Lamellar double hydroxides (LDH) are a class of inorganic materials widely used as pharmaceutical ingredients. However, their use as excipients and mainly as drug carriers lacks specific research in pharmaceutical technology, as there are no publications capable of defining the behavior of these materials as components of a formulation in the presence of other pharmaceutical adjuvants already consolidated. The purpose of the study was to evaluate the excipient–excipient compatibility of calcium and aluminum LDH (LDH–CaAl) against other excipients, including colloidal silicon dioxide (aerosil®), soluble starch (SS), microcrystalline cellulose 101 (MCC), magnesium stearate (MS), hydroxypropyl-beta-cyclodextrin (HPβCD), lactose monohydrate (LACM), sodium starch glycollate (SSG), PVP-K30 and talc. Initially, absorption spectroscopy in the infrared region with Fourier transform (FTIR) and thermogravimetry and differential thermal analysis (TG/DTA) was performed. When signs of possible interactions were observed, X-ray diffraction (XRD) was performed as a complementary technique. At the end of the study, the FTIR spectra and the TG curves of LDH–CaAl and each of the isolated excipients were compared with the analysis of the binary mixtures, where there is compatibility between LDH–CaAl and all excipients tested. Although the XRD has been used to assess evidence of interactions in mixtures with stearate, lactose, PVP and talc, the joint analysis of the results proved to be satisfactory. All these pioneering results suggest, therefore, the acceptability and suitability of LDH–CaAl as a potentially scalable excipient for the development of safe and rational dosage forms. [ABSTRACT FROM AUTHOR]

Ocular drug delivery is very challenging and fascinating for pharmaceutical researchers, especially in the treatment of ocular conjunctivitis. The challenges include delivery of the drug to the eye without causing permanent tissue damage while maintaining a stable therapeutic level at the site of action for a prolonged period of time. The present work focuses on the treatment of ocular conjunctivitis by using combined mechanisms of fluroquinolone antibiotics, providing sustained release of drug from ocular inserts, and using corticosteroid for anti-inflammatory effect and providing comfort to the patient. Quinolone antibiotics, anti-inflammatory agents and polymers with excipients were procured from pharmaceutical companies as gift samples. Different combinations of antibiotics and anti-inflammatory agents were prepared by solvent cast method and the dried films were cut into defined size containing drug and evaluated for different parameters and sustained drug release. Based on in vitro, in vivo correlation stability studies, the formulation (antibiotic + anti-inflammatory agent) promising the best once a day sustained release of the drug has been chosen. [ABSTRACT FROM AUTHOR]

The study aimed to develop and evaluate a liquid self-emulsifying formulation loaded with Nimodipine, focusing on solubility, emulsification, and in vitro release characteristics. Various excipients were screened, and Capmul MCM was selected as the oil phase due to its high solubilization capacity. Surfactants such as Tween 80 and cosurfactants like PEG 400 were chosen based on their emulsification effectiveness. Pseudo-ternary phase diagrams were constructed to optimize the formulation, with formulation F7 being identified as the optimized batch. This formulation exhibited excellent thermodynamic stability, rapid self-emulsification, minimal globule size, and high transmittance. In vitro release studies showed sustained drug release, indicating potential for improved bioavailability. Pharmacokinetic analysis revealed enhanced efficacy compared to a marketed tablet. The developed self-emulsifying drug delivery system shows promise for enhancing the oral delivery and therapeutic efficacy of Nimodipine formulations. [ABSTRACT FROM AUTHOR]

This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances. The commentary first canvasses how contaminants enter the excipient supply chains. One way is by misleading labeling or intentional adulteration by manufacturers or suppliers. Another way is by human or systemic error. This commentary then discusses quality control testing and suggests the ethical and clinical importance of increased transparency in excipient supply chains. [ABSTRACT FROM AUTHOR]

The article discusses the quality issues surrounding herbal dietary supplements, highlighting concerns such as the presence of adulterants like maltodextrin, the absence of active botanical compounds in some products, and the practice of selling extracts diluted with fillers to meet extract ratio requirements. It also discusses the discrepancy between label claims and actual product content, raising questions about the efficacy and safety of these supplements.

Pharmaceutical development of solid-state formulations requires testing active pharmaceutical ingredients (API) and excipients for uniformity and stability. Solid-state properties such as component distribution and grain size are crucial factors that influence the dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared microscopy and confocal Raman spectroscopy are capable of high chemical and spatial resolution but cannot achieve the measurement speeds necessary for integration into the pharmaceutical production and quality assurance processes. To fill this gap, we demonstrate fast chemical imaging by epi-detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution. [ABSTRACT FROM AUTHOR]

The design, development, and release kinetics of omeprazole (OME) from solid dosage forms have been investigated. These formulations were examined for their resilience in pH = 4.5 buffer solutions and their rate of disintegration in a small-intestine-like environment (pH = 6.8). The results were compared with those of the well-known brand product Losec®, where its use is accompanied by numerous benefits but drawbacks as well. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) tests were conducted in order to examine the release kinetics of the various dosage forms and provide explanations based on the interactions between the excipients and the active substance. [ABSTRACT FROM AUTHOR]

Adding certain excipients during the extraction process can enhance the concentration of target compounds, leading to potentially increased biological properties of the plant extract. This study explores the impact of PVP/VAC and SSG excipients on red clover bud extracts, aiming to enhance their concentration of target compounds and, consequently, their biological properties. The antioxidative potential was evaluated using DPPH, ABTS, and FRAP methods, and the chemical profile was determined using mass spectrometry. Antibacterial activity against various strains was determined through the minimal inhibitory concentration (MIC) method. The results revealed that the excipient-enriched samples exhibited significantly elevated antioxidant activities as well as phenolic and flavonoid contents compared to control samples. Notably, sample V1E3 demonstrated the highest antioxidant potential, with 52.48 ± 0.24 mg GAE/g dw (phenolic content), 463 ± 6.46 μg TE/g dw (ABTS), 12.81 ± 0.05 μg TE/g dw (DPPH), and 29.04 ± 1.16 mg TE/g dw (post-column ABTS). The highest flavonoid content was found in the S1E3 sample—24.25 ± 0.17 mg RU/g dw. Despite the increased antioxidant potential, no significant variance in antimicrobial activity was noted between the test samples and controls. This implies that excipients may hold the potential to enhance the biological properties of red clover extracts for pharmaceutical applications. These findings contribute valuable insights into optimizing extraction processes for improved functionality and application of plant-derived compounds in therapeutic formulations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro–in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro–in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality of the final product, this review aims to contribute to a better understanding of the interplay between polymers and pharmaceutical 3DP. As 3DP technologies are increasingly integrated into pharmaceutical sciences, this review contributes insights into the nuanced process of polymer selection, serving mainly as a foundational guide for researchers and formulators new to the subject seeking to harness the full potential of pharmaceutical 3DP by understanding the physicochemical properties, roles, and functions of used polymers in 3D-printed dosage forms and medical devices. [ABSTRACT FROM AUTHOR]

The developments in pharmaceutical excipient science and technology since 1995 have been reviewed. The field of excipients science and technology has changed and continues to change. Some good progress has been made in such areas as harmonization of excipient pharmacopeial monographs, and the application of new analytical methods to better characterize excipients. However, progress in some other areas has been less satisfactory. There have been developments in other areas that have impacted excipients, such as Quality by Design, continuous manufacturing, the preponderance of poorly water-soluble new small molecule drug substances, and the introduction of biologic drug substances. It is likely that these developments will place more demands on our excipients and excipient manufacturers and suppliers. Looking ahead, excipients will continue to be in the spotlight. It is hoped that progress can be made in the development of an independent review of new chemical excipients to ease their introduction. Without new chemical excipients, it seems likely that the robust formulation of some future drug molecules may not be achievable. While new excipients for small molecule drug applications are needed, better and more effective excipients will also be needed for the formulation of biologic drug substances. [ABSTRACT FROM AUTHOR]

Polysorbate 80 is one of the most commonly used surfactants in the formulation of biotherapeutics, particularly those administered intravenously. It comprises a mixture of fatty acids but is not a precisely defined chemical entity. Hence, there are a range of different grades available in the market, all meeting compendial specifications. Polysorbate 80 is known to undergo auto degradation producing protein-damaging by-products, and to contain residual impurities that can have an impact on the stability and integrity of the active ingredients in the formulation. Given the variety of chemical compositions that polysorbate 80 can comprise, the degradation pathway and extent could vary depending on the grade used in the formulation. This study compared the physical and chemical properties of four commercially available polysorbate 80 grades with different degrees of purity and oleic acid content and investigated their degradation profiles. This study did not find any significant differences between the properties or degradation profiles of the four grades investigated. Further studies are underway to understand the formation of other reactive impurities and their impact on the model protein formulations. [ABSTRACT FROM AUTHOR]